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Brain hypometabolic changes in 14 adolescent–adult patients with Niemann–Pick disease type C assessed by 18F-fluorodeoxyglucose positron emission tomography

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Abstract

Objective

Niemann Pick disease type C (NPC) is a rare progressive neurovisceral lysosomal disorder caused by autosomal recessive mutations in the NPC1 or NPC2 genes. 18F-fluorodeoxyglucose (FDG) is a positron-emitting glucose analogue for non-invasive imaging of brain metabolism. FDG PET is commonly used for dementia imaging but its specific application to NPC is rarely described.

Methods

This is a retrospective study of all baseline brain FDG PET performed for NPC patients. Images were assessed using a normal database statistical comparison of metabolic changes expressed in standard deviations and three-dimensional Stereotactic Surface Projection maps. Typical hypometabolic patterns in NPC were identified. We further investigated any correlation between the degree of regional brain hypometabolism and the Iturriaga clinical severity scale.

Results

Brain FDG PET images of 14 adolescent–adult NPC patients were analysed, with mean age of 35 years. We found significant frontal lobe hypometabolism in 12 patients (86%), thalamic hypometabolism in eight patients (57%) and variable parietal lobe hypometabolism in 13 patients (93%). Hypometabolic changes were usually bilateral and symmetric. Ten out of 13 ataxic patients showed cerebellar or thalamic hypometabolism (sensitivity 77%, specificity 100%). Linear regression analysis showed frontal lobe hypometabolism to have the best correlation with the Iturriaga clinical scale (R2 = 0.439; p = 0.01).

Conclusions

We found bilateral symmetric hypometabolism of the frontal lobes, thalami and parietal lobes (especially posterior cingulate gyrus) to be typical of adolescent–adult NPC. Ataxia was commonly associated with cerebellar or thalamic hypometabolism. Frontal lobe hypometabolism showed the best inverse correlation with clinical severity.

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Acknowledgements

We thank Dr Digsu Koye (PhD) from Melbourne EpiCentre for his assistance with statistical analysis.

Funding

None.

Author information

Author notes

  1. TheodoreY. Lau and YungHsiang Kao contributed equally to this work.

Authors and Affiliations

  1. Department of Nuclear Medicine, The Royal Melbourne Hospital, Melbourne, Australia

    Theodore Y. Lau, Yung Hsiang Kao, H. B. Toh, Dinesh Sivaratnam & Meir Lichtenstein

  2. Neuropsychiatry Unit, The Royal Melbourne Hospital, Level 2, John Cade Building, Melbourne, 3050, Australia

    Dennis Velakoulis & Mark Walterfang

  3. Melbourne Neuropsychiatry Centre, University of Melbourne and North Western Mental Health, Melbourne, Australia

    Dennis Velakoulis & Mark Walterfang

  4. Florey Institute of Neuroscience and Mental Health, Melbourne, Australia

    Mark Walterfang

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  1. Theodore Y. Lau
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  2. Yung Hsiang Kao
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  4. Dinesh Sivaratnam
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Correspondence to Mark Walterfang.

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The authors report no competing interests.

Ethical approval

This study was approved by the Melbourne Health Research and Ethics Committee and has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All subjects provided informed consent for the study.

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Lau, T.Y., Kao, Y.H., Toh, H.B. et al. Brain hypometabolic changes in 14 adolescent–adult patients with Niemann–Pick disease type C assessed by 18F-fluorodeoxyglucose positron emission tomography. J Neurol 268, 3878–3885 (2021). https://doi.org/10.1007/s00415-021-10535-4

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  • DOI: https://doi.org/10.1007/s00415-021-10535-4

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